ENST00000542678.5:c.-88+5826G>A

Variant names:

• chr12-122973072-C-T
• rs7296418
• ENST00000542678.5:c.-88+5826G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000542678.5(ABCB9):​c.-88+5826G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,132 control chromosomes in the GnomAD database, including 36,508 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (36499 hom., cov: 32)
  • Exomes 𝑓: 0.73 (9 hom.)
• Consequence: ABCB9 ENST00000542678.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525
• Publications: 49 publications found

Genes affected

ABCB9 (HGNC:50): (ATP binding cassette subfamily B member 9) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This family member functions in the translocation of peptides from the cytosol into the lysosomal lumen. Alternative splicing of this gene results in distinct isoforms which are likely to have different substrate specificities. [provided by RefSeq, Jul 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000542678.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB9	NM_001437843.1		c.-88+1643G>A		intron	N/A	NP_001424772.1
	ABCB9	NM_001438398.1		c.-88+1443G>A		intron	N/A	NP_001425327.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB9	ENST00000542678.5	TSL:1	c.-88+5826G>A		intron	N/A	ENSP00000440288.1
	ABCB9	ENST00000622723.1	TSL:6	n.162G>A		non_coding_transcript_exon	Exon 1 of 1
	ABCB9	ENST00000543935.1	TSL:4	c.-117G>A		5_prime_UTR	Exon 2 of 3	ENSP00000443382.1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105071 AN: 151984 Hom.: 36478 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.689

GnomAD4 exome AF: 0.733 AC: 22 AN: 30 Hom.: 9 Cov.: 0 AF XY: 0.667 AC XY: 16 AN XY: 24

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.875 AC: 7 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.688 AC: 11 AN: 16

Other (OTH) AF: 0.667 AC: 4 AN: 6

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000388202), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.691 AC: 105136 AN: 152102 Hom.: 36499 Cov.: 32 AF XY: 0.690 AC XY: 51308 AN XY: 74358

African (AFR) AF: 0.668 AC: 27719 AN: 41484

American (AMR) AF: 0.696 AC: 10626 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2209 AN: 3470

East Asian (EAS) AF: 0.674 AC: 3484 AN: 5170

South Asian (SAS) AF: 0.587 AC: 2830 AN: 4820

European-Finnish (FIN) AF: 0.718 AC: 7600 AN: 10584

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48358 AN: 67986

Other (OTH) AF: 0.687 AC: 1450 AN: 2112

Alfa AF: 0.698 Hom.: 68980

Bravo AF: 0.686

Asia WGS AF: 0.608 AC: 2117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.51
DANN	Benign	0.70
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7296418; hg19: chr12-123457619;